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Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors

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ClinicalTrials.gov Identifier: NCT01876511
Recruitment Status : Recruiting
First Posted : June 12, 2013
Last Update Posted : March 6, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE June 10, 2013
First Posted Date  ICMJE June 12, 2013
Last Update Posted Date March 6, 2019
Study Start Date  ICMJE September 2013
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2017)
  • Immune-related progression free survival (irPFS) rate at 20 weeks in patients with MSI positive and negative colorectal adenocarcinoma using immune related response criteria (irRC) [ Time Frame: 4 years ]
  • Objective response rate (irORR) at 20 weeks in patients with MSI positive and negative colorectal adenocarcinoma using immune related response criteria (irRC) [ Time Frame: 4 years ]
  • Immune-related progression free survival (irPFS) rate in patients with MSI positive non-colorectal adenocarcinoma using immune related response criteria (irRC) at 20 weeks [ Time Frame: 4 years ]
  • objective response rate in patients with MSI-negative cancer with a mutator phenotype using RECIST 1.1 criteria [ Time Frame: 4 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 10, 2013)
  • Immune-related progression free survival (irPFS) rate at 20 weeks in patients with MSI positive and negative colorectal adenocarcinoma using immune related response criteria (irRC) [ Time Frame: 4 years ]
  • Objective response rate (irORR) at 20 weeks in patients with MSI positive and negative colorectal adenocarcinoma using immune related response criteria (irRC) [ Time Frame: 4 years ]
  • Immune-related progression free survival (irPFS) rate in patients with MSI positive non-colorectal adenocarcinoma using immune related response criteria (irRC) at 20 weeks [ Time Frame: 4 years ]
Change History Complete list of historical versions of study NCT01876511 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2014)
  • Overall survival [ Time Frame: 4 years ]
  • irPFS and PFS in patients with MSI positive and negative tumors at 28 weeks using irRC and RECIST 1.1 [ Time Frame: 4 years ]
  • Best overall response rate and disease control rate in patients with MSI positive and negative tumors [ Time Frame: 4 years ]
  • Number of participants experiencing immune-related toxicities (IRAEs) [ Time Frame: 4 years ]
  • Does MSI as a marker predict treatment response [ Time Frame: 4 years ]
  • Identify alternative markers of MSI status. This includes but is not limited to MLH 1, MSH 2, MSH 6, PMS2, BRAF pV600E, and TGFBR2. [ Time Frame: 4 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2013)
  • Overall survival [ Time Frame: 4 years ]
  • irPFS and PFS in patients with MSI positive and negative tumors at 28 weeks using irRC and RECIST 1.1 [ Time Frame: 4 years ]
  • Best overall response rate and disease control rate in patients with MSI positive and negative tumors [ Time Frame: 4 years ]
  • Number of participants experiencing immune-related toxicities (IRAEs) [ Time Frame: Continuous ]
  • Does MSI as a marker predict treatment response [ Time Frame: 4 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors
Official Title  ICMJE Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors
Brief Summary This study will be looking at whether MK-3475 (an antibody that blocks negative signals to T cells) is effective (anti-tumor activity) and safe in three different patient populations. These include: 1. patients with MSI positive colon cancer, 2. patients with MSI negative colon cancer 3. patients with other MSI positive cancers, and 4. patients with MSI negative cancer with a mutator phenotype.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • MSI Positive Colorectal Cancer
  • MSI Negative Colorectal Cancer
  • MSI Positive Non-Colorectal Cancers
  • High Tumor Mutation Burden
  • High TMB
Intervention  ICMJE
  • Drug: MK-3475
    MK-3475 10 mg/kg every 14 days
  • Drug: MK-3475
    MK-3475 200mg flat dose every 21 days
Study Arms  ICMJE
  • Experimental: MSI Positive Colorectal Cancer
    Intervention: Drug: MK-3475
  • Experimental: MSI Negative Colorectal Cancer
    Intervention: Drug: MK-3475
  • Experimental: MSI Positive Non-Colorectal Cancer
    Intervention: Drug: MK-3475
  • Experimental: MSI Negative with Mutator Phenotype
    Intervention: Drug: MK-3475
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 9, 2015)
171
Original Estimated Enrollment  ICMJE
 (submitted: June 10, 2013)
71
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Arm 1 only: Patients with microsatellite instability (MSI) positive colorectal cancer
  • Arm 2 only: Patients with MSI negative colorectal cancer
  • Arm 3 only: Patients with MSI positive non-colorectal cancer
  • Arm 4 only: patients with hypermutated MSI negative cancer
  • Have measurable disease
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
  • Adequate organ function as defined by study-specified laboratory tests
  • Must use acceptable form of birth control through the study and for 28 days after final dose of study drug
  • Signed informed consent form
  • Willing and able to comply with study procedures
  • Agree to have a biopsy of their cancer
  • Patients with colon cancer must have received at least two prior cancer therapy regimens.
  • Patients with other cancer types must have received at least one prior cancer therapy
  • Progressive disease

Exclusion Criteria:

  • Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements.
  • Patients who have had chemotherapy or biological cancer therapy within 2 weeks prior to the first dose of study drug
  • Patients who have had radiation within 2 weeks prior to the first dose of study drug
  • Patients who have undergone major surgery within 4 weeks of dosing of investigational agent
  • Patients who have received another investigational product or investigational device within 4 weeks prior to receiving study drug
  • Patients who have received any of the following concomitant therapy: Interleukin-2 (IL-2), interferon, or other non-study immunotherapy regimens, immunosuppressive agents, other investigational therapies or chronic use of systemic corticosteroids within one week prior to first dose of study drug
  • Patients who have received a live vaccine within 4 weeks prior to or after any dose of MK-3475 (exception: inactivated flu vaccines)
  • Patients who have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration
  • Patient who have had prior treatment with anti-PD-1 (anti-programmed cell death protein 1), anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies
  • Patients with history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis, central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin.
  • Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
  • Patients with evidence of interstitial lung disease
  • Systemically active steroid use
  • Patients on home oxygen
  • Patients with oxygen saturation of <92% on room air by pulse oximetry
  • Pregnant or lactating
  • Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
  • Patient with known active central nervous system metastases and/or carcinomatous meningitis.
  • Patients with primary brain tumors.
  • Requires any other form of systemic or localized antineoplastic therapy while on study
  • Has any tissue or organ allograft
  • Patients with history of allogeneic hematopoeitic stem cell transplant
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jane Zorzi 410-614-5818 jzorzi1@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01876511
Other Study ID Numbers  ICMJE J1365
MK-3475-016 ( Other Identifier: Merck )
NA_00085756 ( Other Identifier: JHMIRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Dung Le, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP